Clinical safety, tolerability, and pharmacokinetics of murine monoclonal antibody to human tumor necrosis factor-alpha.

ABSTRACT

The safety, tolerability, and pharmacokinetic profile of murine monoclonal antibody to human tumor necrosis factor-alpha (TNF alpha MAb) were evaluated in 20 uninfected patients at risk of sepsis and 16 septic patients. TNF alpha MAb was well tolerated in all patients, with no immediate or delayed signs of allergic reaction. During the 28-day evaluation, side effects included thrombocytosis (11), hepatic enzyme elevations (8), cardiac arrhythmias (3), and deaths (5). Each was attributed to the patient's severe underlying disease and not to TNF alpha MAb; however, a relationship between TNF alpha MAb and these events cannot be ruled out. The half-life was 52 h for a single infusion of TNF alpha MAb. Human antibody against TNF alpha MAb was observed in 13 (76.5%) of 17 phase IA patients and 10 of 10 phase IB patients and anti-idiotype antibodies in 11 (91.7%) of 12 phase IA patients and 2 (33.3%) of 6 phase IB patients. TNF alpha MAb should be evaluated as adjunctive therapy for patients with sepsis.